Failure of pancreatic polypeptide release in congenitally obese mice

Obesity can be reversed in ob/ob mice by parabiosis to lean littermates, by islet transplantation, and by injection of pancreatic polypeptide. These observations suggest that obese mice have functioning satiety centers but lack a circulating satiety factor of pancreatic origin which could be pancreatic polypeptide. This hypothesis has been difficult to test because antisera currently available do not cross-react with rodent pancreatic polypeptide. We have raised an antiserum against the biologically active carboxyl-terminal hexapeptide that measures mouse pancreatic polypeptide specifically. This antiserum has been used to compare circulating and tissue concentrations of pancreatic polypeptide in obese and lean mice. Although pancreatic contents were significantly (p less than 0.01) increased in obese mice (237 +/- 34 pmol/g) compared with lean littermates (107 +/- 20 pmol/g), no postprandial increase in circulating concentrations was observed in obese mice. The hypothesis that obese mice lack a satiety factor of pancreatic origin could be explained by the failure of release of pancreatic polypeptide.